DPT Report 2006 - ERNDIM

Sample C
Patient: The urine sample was obtained from a 23 year old female who had first presented at the
age of 5 years due to episodic vomiting, hypoglycaemia and loss of consciousness. She has
remained essentially well on treatment and the urine was collected at the age of 23 whilst
asymptomatic. The diagnosis was confirmed by enzyme assay on skin fibroblasts. Treatment had
included avoidance of fasting, frequent meals and intermittently carnitine.
Analytical performance: Nineteen laboratories analysed organic acids and correctly identified
one or more key acyl glycines leading to the correct diagnosis of MCAD deficiency. The remaining
laboratory did analyse organic acids but reported a normal finding. The analytical performance of
this sample was high (95%)
Interpretative proficiency: The diagnosis of medium chain acylCoA dehydrogenase deficiency
was considered correct. 19 labs concluded the correct diagnosis so that the interpretative
proficiency for this sample was excellent (95%).
Recommendations: follow up by measuring acyl carnitines in blood and or enzyme assay and or
mutation analysis was considered correct.
Quantitative data:
• Creatinine:
0.52; 5.21; 5.3; 5.39; 5.42; 5.44; 5.48; 5.5; 5.6; 5.64; 5.68; 5.75; 5.89; 5.9; 6.07;
6.19; 6.2; 6.4; 6.45; 6.8 (mmol/l), mean 5.54, median 5.66.
• Organic Acids:
Hexanoylglycine:
3.3; 9; 27; 31; 35; 42; 117; (mmol/mol creatinine); 39.03 (µg/mg creatinine)
Phenylproprionylglycine:
5; 7; 17 (mmol/mol creatinine); 21.42 (µg/mg creatinine)
Suberylglycine:
6; 27; 31; 40; 42; 80; 262; (mmol/mol creatinine); 93.76 (µg/mg creatinine)
Sample D
Patient: The sample was obtained at 3 ½ years of age from a now 5½ year old boy with
dihydropyrimidine dehydrogenase deficiency. The diagnosis was based on examination of urine,
plasma and CSF organic acids. The diagnosis was confirmed at the AMC Amsterdam by enzyme
assay and mutation analysis.
Analytical performance: 18 Laboratories reported organic acid analysis and 16 were able to
correctly identify the metabolites indicative of dihydropyrimidine dehydrogenase deficiency. Two
laboratories did not report these abnormalities but did make the correct diagnosis by purine and
pyrimidine analysis. In all 13 laboratories analysed purines and pyrimidines all reporting abnormal
metabolite(s). A correct diagnosis but lack of abnormalities on organic acid analysis was
considered as only partially satisfactory performance.
The analytical performance of this sample was 94%.
Interpretative proficiency: Diagnosis of thyminuria / uraciluria due to dihydropyrimidine
dehydrogenase deficiency was considered correct. The proficiency score of 97% was very
satisfactory.
Recommendations: In our opinion the most important advice for follow-up investigation was
confirmation of the defect by enzyme assay and possible mutation analysis. When at least one of
these two follow up measures was given the recommendations were considered helpful.
Overall impression: the total overall score of 93% indicates very satisfactory performance for this
defect.
Quantitative data:
• Creatinine: 2.65; 2.74; 2.82; 2.99; 3.10; 3.2; 3.2; 3.3; 3.36; 3.4; 3.49; 3.54; 3.66;
3.7; 3.7; 3.84; 4.0 (mmol/l), mean 3.3, median 3.4.
• Organic Acids:
Uracil: 101; 241; 600; 612; 722; 847; (mmol/mol creatinine)
Thymine: 184.3; 393; 461; 666; 1100; (mmol/mol creatinine)
• Purines/Pyrimidines:
ERNDIM DPTC Basel – Annual Report 2006, page 4